---------------------------SLEEP DISORDERS: OVERVIEW--------------------------- STATEMENT Sleep disturbances occur in about 12 to 25% of the general population in industrialized countries,[1] often associated with situational stress, illness, aging, and drug treatment.[2] Approximately 45% of people with cancer have been found to have a higher incidence of sleep disturbances than that of either a general population or persons with nonmalignant medical conditions.[3] Physical illness, pain, hospitalization, and the psychological impact of a malignant disease may disrupt the sleeping patterns of persons with cancer. Poor sleep adversely affects daytime mood and performance. In the general population, persistent insomnia has been associated with a higher risk of developing clinical anxiety or depression. Adequate sleep may increase the cancer patient's pain tolerance. Sleep consists of two phases: rapid eye movement (REM) and non-REM (NREM) sleep.[4] REM sleep, also known as "dream sleep", is the active or paradoxic phase of sleep, in which the brain is active while the body is essentially paralyzed. NREM is the quiet or restful phase of sleep. NREM, also referred to as slow wave sleep, is divided into four stages of progressively deepening sleep based on EEG findings.[2,5] The stages of sleep occur in a repeated pattern or cycle of NREM followed by REM, with each cycle lasting approximately 90 minutes. The sleep cycle is repeated 4 to 6 times during a 7 to 8 hour sleep period.[5] Each cycle consists of most or all of the stages of NREM followed by REM. The sleep-wake cycle is dictated by an inherent biological clock or circadian rhythm. Disruptions in individual sleep patterns can disrupt the circadian rhythm and impair the sleep cycle.[6] Four major categories of sleep disorders have been defined by the Sleep Disorders Classification Committee: 1) disorders of initiating and maintaining sleep (insomnias) 2) disorders of the sleep-wake cycle 3) dysfunctions associated with sleep, sleep stages, or partial arousals (parasomnias) 4) disorders of excessive somnolence. References: 1. Walsleben J: Sleep disorders. American Journal of Nursing 82(6): 936-940, 1982. 2. Kaempfer SH: Comfort: Sleep. In: Johnson BL, Gross J, Eds.: Handbook of Oncology Nursing. New York: John Wiley & Sons, 1985, pp 167-184. 3. Beszterczey A, Lipowski ZJ: Insomnia in cancer patients (letter). Canadian Medical Association Journal 116(4): 355, 1977. 4. Guyton AC.: Textbook of Medical Physiology. Philadelphia: WB Saunders, 7th ed., 1986. 5. Feirerman JR: Disordered sleep. Emergency Medicine 2: 160-171, 1985. 6. Taub JM, Berger RJ: The effects of changing the phase and duration of sleep. Journal of Experimental Psychology: Human Perception and Performance 2(1): 30-41, 1976. SLEEP DISORDERS: SLEEP DISTURBANCE IN CANCER PATIENTS Cancer patients are at great risk for developing insomnias and disorders of the sleep-wake cycle. Insomnia is the most common sleep disturbance in this population, and is most often secondary to physical and/or psychological factors related to cancer and/or cancer treatment. Anxiety and depression, common psychological responses to the diagnosis of cancer, cancer treatment, and hospitalization, are highly correlated with insomnia.[1-3] Psychological stress of having cancer is the most common psychological cause of insomnia. Physical factors related to cancer include paraneoplastic syndromes associated with steroid production, symptoms associated with tumor invasion (draining lesions, GI and GU alterations, pain, obstruction, fever, cough, dyspnea), pruritus, and fatigue. Treatment-related factors include surgical pain, administration of corticosteroids as chemotherapeutic agents, and symptoms associated with treatment such as nausea, vomiting, frequent elimination, and fatigue.[4] Side effects of treatment that may affect the sleep-wake cycle include:[5] -pain -tension -anxiety -night sweats -GI disturbances (i.e., incontinence, diarrhea, constipation) -GU disturbances (i.e., incontinence, retention, GU irritation) -respiratory disturbances Hypnotic drugs can also cause insomnia in cancer patients. Insomnia is produced by tolerance to or withdrawal from a wide variety of hypnotic agents and other central nervous system depressants. Sustained use of central nervous system stimulants (e.g., amphetamines, caffeine, diet pills), hypnotics (e.g., glutethimide, pentobarbital, chloral hydrate, secobarbital sodium, amobarbital sodium), cancer chemotherapeutic agents (especially antimetabolites), anticonvulsants (e.g., phenytoin), adrenocorticotropin, oral contraceptives, monoamine oxidase inhibitors, alpha-methyldopa, propranolol, atenolol, alcohol, and thyroid preparations can cause insomnia. In addition, withdrawal from central nervous system depressants (barbiturates, glutethimide, chloral hydrate, methaqualone, ethchlorvynol, alcohol, over-the-counter and prescription antihistamine sedatives, and bromides), benzodiazepines, major tranquilizers, tricyclic and monamine oxidase inhibitor antidepressants, illicit drugs (e.g., marijuana, cocaine, phencyclidine, opiates), and agents containing aspirin may cause insomnia. The most commonly prescribed hypnotics interfere with REM sleep resulting in increased irritability, apathy, and diminished mental alertness. Abrupt withdrawal of hypnotics may lead to many symptoms including nervousness, jitteriness, and REM rebound. Berlin defined REM rebound as a "marked increase in REM sleep with increased frequency and intensity of dreaming, including nightmares."[6] The increased physiologic arousal that occurs during REM rebound may be dangerous for patients with peptic ulcers or a history of cardiovascular problems. Hospitalized patients are likely to experience frequent interruptions of sleep due to treatment schedules, hospital routines, and roommates, which singularly or collectively alter the sleep-wake schedule. Other factors influencing sleep-wake schedules in the hospital setting include age, noise, temperature, comfort, pain, and anxiety.[7] Consequences of sleep disturbances can influence outcomes of medical and supportive care measures. The patient with mild to moderate sleep disturbances might experience irritability and inability to concentrate, which may in turn affect the patient's compliance with treatment protocols, ability to make decisions, and relationships with significant others. Depression and anxiety can also be end-results of sleep disturbances. Supportive care measures are directed toward quality of life issues and promote adequate rest. References: 1. Coursey RD: Personality measures and evoked responses in chronic insomniacs. Journal of Abnormal Psychology 84(3): 239-249, 1975. 2. Freemon FR: Sleep Research: A Critical Review. Springfield, IL: Thomas Publishing, 1972. 3. Johns MW, Bruce DW, Masterton JP: Psychological correlates of sleep habits reported by healthy young adults. British Journal of Medical Psychology 47(2): 181-187, 1974. 4. Clark J, Landis L, McGee R: Nursing management of outcomes of disease, psychological response, treatment, and complications. In: Ziegfeld CR, Ed.: Core Curriculum for Oncology Nursing. Philadelphia: W.B. Saunders, 1987, pp 271-319. 5. Page M: Sleep pattern disturbance. In: McNally JC, Stair JC, Somerville ET, Eds.: Guidelines for Cancer Nursing Practice. Orlando, FL: Grune and Stratton, Inc., 1985, pp 89-95. 6. Berlin RM: Management of insomnia in hospitalized patients. Annals of Internal Medicine 100(3): 398-404, 1984. 7. Webster RA, Thompson DR: Sleep in hospital. Journal of Advanced Nursing 11(4): 447-457, 1986. MANAGEMENT OF SLEEP DISTURBANCES: ASSESSMENT Assessment is the initial step in management strategies. Assessment data will include predisposing factors, sleep patterns, emotional status, exercise and activity level, diet, symptoms, medications, and caregiver routines.[1] The sections below outline recommendations for a sleep history and physical examination. Data can be retrieved from multiple sources including the patient's subjective report of sleep difficulty, objective observations of behavioral and physiologic manifestations of sleep disturbances, and reports from the patient's significant others regarding the patient's quality of sleep.[2] --Sleep history assessment-- Risk factors The following factors may increase risk for sleep disorders: -disease factors including paraneoplastic syndromes with increased steroid production; symptoms associated with tumor invasion (e.g., obstruction, pain, fever, shortness of breath, pruritus, fatigue); -treatment factors including symptoms related to surgery (e.g., pain, frequent monitoring, narcotics); chemotherapy (e.g., exogenous corticosteroids); symptoms related to chemotherapy -medications such as narcotics, sedatives/hypnotics, steroids, caffeine/nicotine -environment -physical and/or psychological stress -depression -anxiety Characterization of sleep The following should be assessed in taking a sleep history: -usual patterns of sleep, including usual bedtime, routine prior to retiring (e.g., food, bath, medications), length of time before onset of sleep, and duration of sleep (awaking episodes during night, ability to resume sleep, and usual time to awaken) -characteristics of disturbed sleep (changes following diagnosis, treatment, and/or hospitalization) -perception of significant others on quantity and quality of patient's sleep -family history of sleep disorders References: 1. Kaempfer SH: Insomnia. In: Baird SB, Ed.: Decision Making in Oncology Nursing. Philadelphia: B.C. Decker, Inc., 1988, pp 78-79. 2. Kaempfer SH: Comfort: Sleep. In: Johnson BL, Gross J, Eds.: Handbook of Oncology Nursing. New York: John Wiley & Sons, 1985, pp 167-184. MANAGEMENT OF SLEEP DISTURBANCES: MANAGEMENT STRATEGIES Management of sleep disturbances should focus on treatment of the underlying malignancy and the identification and management of environmental and psychological factors. Management of sleep disturbances combines non-pharmacologic and pharmacologic approaches individualized for the patient. Treatment of the malignancy may resolve the sleep disturbance. When sleep disturbances are caused by symptoms of cancer or treatment, measures that control or alleviate symptoms are often the key to resolving sleep disturbances. Non-pharmacologic strategies The environment can be modified to decrease sleep disruption. Minimizing noise, dimming or turning off lights, adjusting room temperature, and consolidating patient care tasks to decrease interruptions can increase the amount of uninterrupted sleep. Other actions or interventions that may promote rest include: [1,2] -keeping the patient's skin clean and dry -giving backrubs and/or massaging areas of the body the patient might find comforting (e.g., bony prominences, head and scalp, shoulders, hands, feet) -keeping bedding and/or surfaces of support devices (chairs, pillows) clean, dry, and wrinkle-free -ensuring adequate bedcovers for warmth -regulating fluid intake to avoid nocturia -encouraging bowel and bladder elimination before sleep -promoting optimal bowel function (increased fluids, fiber in diet, use of stool softeners and laxatives) -using condom catheter for nocturnal incontinence -providing high protein bedtime snack -avoiding beverages with caffeine -encouraging patient to dress in loose, soft clothing -facilitating comfort through repositioning and support with pillows as needed -encouraging exercise or activity no less than 2 hours before bedtime -providing a light snack -keeping regular bedtime and awakening hours Psychological interventions are directed toward facilitating the patient's coping processes through education, support, and reassurance. As the patient learns to cope with the stresses of illness and hospitalization, sleep may improve.[3] Communication and verbalization of concerns, and openness between the patient, family, and health care team should be encouraged. Pharmacologic management of sleep disturbances When sleep disturbances are not resolved with other supportive care measures, the use of sleep medications on a short-term or intermittent basis may be necessary. However, prolonged use of sleep medications for persistent insomnia can impair natural sleep patterns (i.e., REM deprivation) and alter physiologic functions. Prolonged use (>1 to 2 weeks) may result in tolerance, psychological and physical dependence, drug intoxication, and drug hangover.[4] Agents used in the management of sleep disturbances are included in Table 1. Benzodiazepines are currently the drug of choice in the management of sleep disturbances. Used as an adjunct to other treatment for short periods of time, these agents are safer and more effective in producing natural sleep because they are less disruptive of REM sleep than other hypnotic agents. Benzodiazepines have an anti-anxiety effect in low doses and a hypnotic effect in high doses. Benzodiazepines differ from each other in duration of action and pharmacokinetics. Long-acting benzodiazepines are characterized by: 1) half-lives > 24 hours 2) pharmacologically active metabolites 3) accumulation with multiple dosages, and 4) impaired clearance in the elderly and those with liver disease. Intermediate- and short-acting benzodiazepines have half-lives from 4 to 24 hours. Active metabolites are uncommon in short-acting benzodiazepines, accumulation with multiple doses is rare, and age and liver disease have a minimal effect on drug clearance. While long-acting agents may produce daytime hangover, short-acting agents are more often associated with dependence, rebound insomnia, early morning insomnia, daytime anxiety, and serious withdrawal effects such as seizures.[3] In general, non-benzodiazepines should be reserved for patients who cannot tolerate benzodiazepines. Antihistamines have become popular drugs for the management of sleep disturbances among cancer patients. The anticholinergic properties of antihistamines relieve nausea and vomiting as well as insomnia. These agents must be used with caution since daytime sedation and delirium can occur. Tricyclic antidepressants, such as amitriptyline or doxepin, may be effective in patients who are depressed. When given at bedtime, they can eliminate the need for an additional hypnotic. The hypnotic effects of marijuana (tetrahydrocannabinol or THC) are similar to conventional hypnotics in reducing REM sleep. Side effects prior to sleep induction and hangover make the THC less acceptable than benzodiazepines.[5] Alcohol used in moderation may decrease tension and promote sleep in some patients. Aspirin is believed to promote sleep onset through increasing serotonin action, which is thought to enhance the onset of sleep without disrupting the normal sleep cycle.[4] Barbiturates are generally not recommended for the management of sleep disturbances in cancer patients. Barbiturates have a number of adverse effects, including the development of tolerance, and they also have a narrow margin of safety. Most hypnotics are effective initially, but lose efficacy when used regularly. Patients can become dependent upon a hypnotic after only one week of regular use. Sleep medications can become a primary cause of sleep disturbances.[6] TABLE 1: MEDICATIONS USED TO PROMOTE SLEEP drug category medication hypnotic dose onset (duration (route) of action) ------------- ---------- ------------- --------------- benzodiazepines diazepam 5-10 mg (capsule, 30-60 min (Valium) tablet) (6-8 hours) flurazepam 15-30 mg 1 hr (Dalmane) (capsule) (24 hrs) lorazepam 2-4 mg highly (Ativan) (capsule) individual oxazepam 10-30 mg shorter than (Serax) (capsule, diazepam tablet) temazepam 15-30 mg 30 min (Restoril) (capsule) (6-8 hrs) triazolam 0.125-0.5 mg shorter than (Halcion) (tablet) flurazepam (peaks 1-1.5 hours) chloral chloral hydrate 0.5-1.0 g 30-60 min derivatives (capsule, syrup, (4-8 hrs) suppository) acetylinic ethchlorvynol 0.5-1.0 g 15-30 min alcohol (Placidyl) (capsule) (4-5 hrs) piperidinedione glutethimide 250-500 mg 30 min derivatives (Doriden) (capsule, (4-8 hrs) tablet) antihistamines diphenhydramine 50-100 mg 10-30 min (Benadryl) (tablet, capsule, (4-6 hrs) syrup) hydroxyzine 25-100 mg 15-30 min (Vistaril, (tablet, capsule, (4-6 hrs) Atarax) syrup) promethazine 25-50 mg 20 min (Phenergan) (capsule, (4-6 hrs) tablet, syrup, suppository) References: 1. Page M: Sleep pattern disturbance. In: McNally JC, Stair JC, Somerville ET, Eds.: Guidelines for Cancer Nursing Practice. Orlando, FL: Grune and Stratton, Inc., 1985, pp 89-95. 2. Kaempfer SH: Insomnia. In: Baird SB, Ed.: Decision Making in Oncology Nursing. Philadelphia: B.C. Decker, Inc., 1988, pp 78-79. 3. Berlin RM: Management of insomnia in hospitalized patients. Annals of Internal Medicine 100(3): 398-404, 1984. 4. Kaempfer SH: Comfort: Sleep. In: Johnson BL, Gross J, Eds.: Handbook of Oncology Nursing. New York: John Wiley & Sons, 1985, pp 167-184. 5. Hollister LE: Health aspects of cannabis. Pharmacological Reviews 38(1): 1-20, 1986. 6. Hayter J: Advances in sleep research: implications for nursing practice. In: Tierney AJ, Ed.: Recent Advances in Nursing: Clinical Nursing Practice. Edinburgh, Scotland: Churchill Livingstone, 1986, pp 21-43. SLEEP DISORDERS: SPECIAL CONSIDERATIONS The patient with pain The experience of pain may be heightened by the use of sleep medications. Analgesics or non-pharmacologic pain management should be administered before sleep medications. The elderly Elderly patients frequently have insomnia due to age-related changes in sleep. The sleep cycle in this population is characterized by lighter sleep, more frequent awakenings, and less total sleep time. Anxiety, depression, loss of social support, and a diagnosis of cancer are contributory factors in sleep disturbances in the elderly.[1] Providing a regular schedule of meals, discouraging daytime naps, and encouraging physical activity may improve sleep. Hypnotic prescriptions for elderly patients must be adjusted for variations in metabolism and increased sensitivity. Dosages should be reduced by 30 to 50% (e.g., flurazepam 15 mg, temazepam 15 mg, and triazolam 0.125 mg). Problems associated with drug accumulation (especially flurazepam) must be weighed against the risks of more severe withdrawal or rebound effects associated with short-acting benzodiazepines. An alternate drug for elderly patients is chloral hydrate.[1] Somnolence syndrome Cranial irradiation and intrathecal methotrexate are used to prevent the development of central nervous system (CNS) leukemia in children with acute lymphocytic leukemia (ALL). Somnolence syndrome (SS) is a complication of cranial irradiation occurring in 30 to 50% of patients who receive over 2400 cGy at daily dose fractions of 150 to 200 cGy. The syndrome may appear 4 to 6 weeks following completion of therapy. SS is characterized by mild drowsiness to moderate lethargy and, occasionally, low-grade fever. The pathophysiology is unknown, but electroencephalogram (EEG) and cerebral spinal fluid abnormalities are detectable in affected children. Whether the occurrence of SS correlates with permanent CNS dysfunction and whether reduced daily fractions affect the incidence or severity of late CNS dysfunction are subjects of current research.[2] While supportive care measures cannot prevent the occurrence of SS, acknowledgement of the existence of this problem may prevent or minimize anxieties for children and parents when symptoms of SS appear." Sleep apnea following mandibulectomy Anterior mandibulectomy can result in the development of sleep apnea. All patients with head and neck tumors who have had extensive anterior oral cavity resection should be evaluated prior to decannulation of the tracheostomy tube. Subsequent flap and/or reconstruction of the lower jaw seems to prevent the development of sleep apnea. In contrast, facial sling suspension of the lower lip does not prevent the development of sleep apnea.[3] Assessment for symptoms and preparation for the appearance of symptoms in this population provide indications for interventions related to sleep apnea. References: 1. Berlin RM: Management of insomnia in hospitalized patients. Annals of Internal Medicine 100(3): 398-404, 1984. 2. Littman P, Rosenstock J, Gale S, et al.: The somnolence syndrome in leukemic children following reduced daily dose fractions of cranial radiation. International Journal of Radiation Oncology, Biology, Physics 10(10): 1851-1853, 1984. 3. Panje WR, Holmes DK: Mandibulectomy without reconstruction can cause sleep apnea. Laryngoscope 94(12, Part 1): 1591-1594, 1984.